This research proposal developed from preliminary observations on a GSH-peroxidase from liver. In contrast to the RBC enzyme and the liver enzyme already reported by others, this enzyme is much more stable when purified, does not require activation by preincubation with 25 mM GSH, shows saturation kinetics with GSH (Km=75 micron M), does not show saturation with cumene hydroperoxide, and has a molecular weight of 43,000. We believed that either liver enzyme was somewhat different from the more thoroughly characterized RBC enzyme, that there might be two enzymes in the liver, one cytosolic and one mitochondrial which had not been sufficiently studied, or that essentially all RBC enzyme and liver enzyme preparations which have been studied in greater detail have been modified from the native enzyme by organic solvents used. Originally we considered that our enzyme might be one of a family of selenoenzymes. Lawrence and Burk, Federation Proceedings 35, No. 3 (1976) p.598 (Abstract No. 2060) reported GSH-Peroxidase with molecular weight similar to the one we began to study. The 43,000 mol. wt. enzyme is now known as GSH-Peroxidase II and may not contain selenium. The possible identity of GSH Peroxidase II with one or more of the GSH-S-transferases of Jakoby et al. (J.B.C. 251, 6183 (1976) in rat liver and in guinea pig liver is under active investigation by seeking highly purified preparations. Since the proposed function of GSH-peroxidase is to protect active membranes from destruction by lipid peroxide formation, a thorough study of both cytosolic and mitochondrial enzymes in many tissues should seem to be in order. GSH-peroxidase is known to be low in some hemolytic conditions of possibly genetic origin, in newborn, and in selenium deficiency. The full pathological implications in all tissues are not yet known, as Vitamin E can in part prevent expression of GSH-peroxidase deficiency.